Chaetocin, a natural product from Chaetomium species, is a histone methyltransferase inhibitor with IC50 of 0.8 μM, 2.5 μM and 3 μM for dSU (VAR)3-9, mouse G9a and Neurospora crassa DIM5, respectively. It also inhibits thioredoxin reductase (TrxR) with an IC50 of 4 μM.
Histone methylation plays a key role in establishing and maintaining stable gene expression patterns during cellular differentiation and embryonic development. Some histone methyltransferases (HMTs) are misregulated in tumors and methyltransferase-induced heterochromatin formation is related to neurodegenerative diseases. Histone methyltransferase SU(VAR)3-9 plays an critical role in establishing condensed heterochromatin by specifically methylating Lys9 of histone H3 and is conserved in most higher eukaryotes. Chaetocin, produced by Chaetomium sp, is a specific inhibitor of SU(VAR)3-9 with IC50 value of 0.8 uM, and also inhibits known Lys9-specific HMTs such as mouse G9a and Neurospora crassa DIM5 with IC50 values of 2.5 and 3 mM, respectively[3]. Mice, bearing mouse hepatoma cell line Hepa 1c1c-7 tumors, showed significant retarded tumor growth after intraperitoneally administrating with chaetocin at 0.25 mg/kg daily for 2 weeks. The hypoxic induction of HIF-1a was decreased in human hepatoma cell lines HepG2, Hep3B, and Huh7 when pretreated with chaetocin (0.05 and 0.1 uM) 1h prior to normoxic or hypoxic incubation for 8h[4]. Chaetocin at 10 - 30 nM inhibited IBMX-induced melanin synthesis in a dose-dependent manner which was relieved by suppression of ERK pathway[5].
Chaetocin/毛壳素 细胞研究
细胞系
浓度
检测类型
检测时间
活性说明
数据源
A549 cells
Cytotoxicity assay
Cytotoxicity against human A549 cells, IC50=0.025 μM
20303767
Hep3b cells
Function assay
Inhibition of HIF-1alpha-mediated VEGF expression in human Hep3b cells by luciferase reporter gene assay, IC50=0.04 μM
22305612
HL60 cells
0.3 uM
Function assay
4 h
Induction of apoptosis in human HL60 cells assessed as nuclear fragmentation at 0.3 uM after 4 hrs using DAPI/PI by confocal laser microscopy analysis
20675131
Jurkat cells
Cytotoxicity assay
40 h
Cytotoxicity against human Jurkat cells after 40 hrs bioluminescence assay, IC50=0.6 μM
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